THE CELL CYCLE AND CANCER

OK…what tells a cell when to divide (or, indeed, when NOT to divide)?

Control of the Cell cycle Control of the cell cycle

Cell cycle controls

Cell cycle regulators Special proteins regulate the timing of the cell cycle in eukaryotic cells They are sometimes called internal regulators – proteins that respond to events inside the cell They direct cells to speed up or slow down the cell cycle They prevent excessive cell growth and prevent tissues from disrupting each other

OK…what tells a cell when to divide (or, indeed, when NOT to divide)? Let's get some help from the NOBEL organisation... Let's get some help from the NOBEL organisation... and how about some help from Harvard? Animation

What is cancer and how does it start? Take 5 minutes and silently write down your ideas.

Your Ideas Mutated cell Continues to divide Can be spread through the blood Due to failure of checkpoint controls Failure of apoptosis

What causes cancer?

What types of cancer are there?cancer

Development of a Tumor from the Howard Hughes Medical Institute Angiogenesis

An introduction to the biology of cancer Cold Harbour website

Cell division and cancer Which karyotype is the bladder cancer cell?

This representative karyotype from a human prostate cancer cell line before injection into nude mice shows all human chromosomes with characteristic marker chromosomes

How do cancer cells differ from normal cells?

What’s the link between control of the cell cycle and cancer? In cancer, defective cell cycle control means that parts of chromosomes are lost, rearranged or unequally distributed between daughter cells This is typically due to mutation(s) [‘damage’]to cell cycle regulator proteins ‘Broken’ genes for cell cycle regulators keeps cell division going continuously) Increased levels of faulty cell cycle regulators are often identified in human cancer cells (e.g. skin, breast)

Gene mutation Definition: A random change in genetic material Mutation can be due to dysfunction during DNA replication (‘copying errors’ of DNA, OR external damage to DNA ‘Mutation is the destroyer and creator of life’ ‘… the fuel for the Darwinian factory’ ‘Thanks to mutation, we’re not all still in the primordial soup’

Causes of mutation (1): ‘Internal causes’ Copying error during DNA replication (Not noticed/corrected at checkpoints) Intra-cellular mutagenic chemicals (free radical molecules) DNA damage

Causes of mutation (2): External causes Radiation Chemicals Viruses Diet Stress Lifestyle ‘Hiroshima – the most cynical Biology experiment of all time’

Types of mutation here's an animated summary...

Oncogenes and tumour suppressor genes Mutated Oncogenes act like accelerators stuck to the floor of the cell cycle. Only ONE oncogene needs to be mutated to make the cell divide continuously Tumour suppressor genes act like the BRAKES on the cell cycle. It is necessary to alter BOTH copies of the gene to get rid of the brake

P53: the most frequently altered gene in human cancers

p53 from Howard Hughes p53 movie cancer treatment using the common cold!

How does cancer compare to other causes of death in the developed world? What percentage of all deaths is attributed to cancer?

Switzerland, 2010

2007 Estimated US Cancer Deaths* ONS=Other nervous system. Source: American Cancer Society, Men 289,550 Women 270,100 26%Lung & bronchus 15%Breast 10%Colon & rectum 6%Pancreas 6%Ovary 4%Leukemia 3%Non-Hodgkin lymphoma 3%Uterine corpus 2%Brain/ONS 2% Liver & intrahepatic bile duct 23% All other sites Lung & bronchus31% Prostate9% Colon & rectum 9% Pancreas6% Leukemia4% Liver & intrahepatic4% bile duct Esophagus4% Urinary bladder3% Non-Hodgkin 3% lymphoma Kidney3% All other sites 24%

Cancer is a lot more than just genes…. Tobacco, the case for primary prevention Infection and cancer: intervention is key Poverty, affluence and the global burden of cancer The Western lifestyle and its health risks

Key Statements from the WHO: Molecular genome research will reveal a tremendous amount of information on cancer but it is not clear how easy these discoveries will translate into actual lives saved and may well be restricted to rare cancers Tobacco use is the major preventable cause of cancer in the world. Behavioral changes in tobacco, alcohol and diet will prevent far more cancers than the elimination of toxins such as industrial pollution, car exhaust and dioxins

Key Statements from the WHO: The Pap smear for cervical cancer is the single best cancer screening procedure. ALLIn 2000, the last year for which global data exists, some 400,000 women died from breast cancer, representing 1.6 per cent of ALL female deaths There are now great genetic tests to screen women for breast cancer risk… A diet high in fruits/vegetables/ low in red meat can lower your risk for cancers of the digestive tract by 25%).